Zoonotic Parasites in Playgrounds in Southern Spain: A One Health Approach.

Zoonotic parasitic diseases are considered a global threat to public health. In this sense, canines and felines may be infected by different cosmopolitan parasites, with playgrounds serving as an important focus of infection for humans, as well as domestic or wild animals. Knowledge of the epidemiological situation of parasites in animal reservoirs integrated into the environment, identifying the spread pathways, is a key element for an effective response to this threat. Thus, the aim of this study was to assess the frequency of intestinal parasites with zoonotic potential in 120 playgrounds in the Malaga province (Spain). Samples were processed and analysed following standard parasitological procedures. Some 36.7% of playgrounds were parasite-positive with one or more zoonotic parasites. The most common parasites recovered were nematodes (60.0%), followed by protozoan species (33.3%) and cestodes (6.7%). In the parasite-positive playgrounds, Toxocara spp. (17.0 ± 3.5%) and Giardia duodenalis (17.0 ± 3.4%) were the most predominant parasites. In addition, 34.1% of playgrounds were infected with multiple parasites. Our results show a high presence of parasitic forms with zoonotic potential in playgrounds in Malaga, Spain. Due to the close contact between pets and humans in playgrounds, the potential zoonotic risk may increase if prevention and control measures are not designed.

Secretory Profile of Adipose-Tissue-Derived Mesenchymal Stem Cells from Cats with Calicivirus-Positive Severe Chronic Gingivostomatitis.

The feline calicivirus (FCV) causes infections in cats all over the world and seems to be related to a broad variety of clinical presentations, such as feline chronic gingivostomatitis (FCGS), a severe oral pathology in cats. Although its etiopathogeny is largely unknown, FCV infection is likely to be a main predisposing factor for developing this pathology. During recent years, new strategies for treating FCGS have been proposed, based on the use of mesenchymal stem cells (MSC) and their regenerative and immunomodulatory properties. The main mechanism of action of MSC seems to be paracrine, due to the secretion of many biomolecules with different biological functions (secretome). Currently, several pathologies in humans have been shown to be related to functional alterations of the patient's MSCs. However, the possible roles that altered MSCs might have in different diseases, including virus-mediated diseases, remain unknown. We have recently demonstrated that the exosomes produced by the adipose-tissue-derived MSCs (fAd-MSCs) from cats suffering from FCV-positive severe and refractory FCGS showed altered protein contents. Based on these findings, the goal of this work was to analyze the proteomic profile of the secretome produced by feline adipose-tissue-derived MSCs (fAd-MSCs) from FCV-positive patients with FCGS, in order to identify differences between them and to increase our knowledge of the etiopathogenesis of this disease. We used high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology to compare the secretomes produced by the fAd-MSCs of healthy and calicivirus-positive FCGS cats. We found that the fAd-MSCs from cats with FCGS had an increased expression of pro-inflammatory cytokines and an altered proteomic profile compared to the secretome produced by cells from healthy cats. These findings help us gain insight on the roles of MSCs and their possible relation to FCGS, and may be useful for selecting specific biomarkers and for identifying new therapeutic targets.

Fermented rye with Agaricus subrufescens and mannan-rich hydrolysate based feed additive to modulate post-weaning piglet immune response.

BACKGROUND: The process of weaning in piglets is often associated with an increased inflammation response in the intestine and compromised intestinal integrity and morphology, favoring a delay in intestinal maturation and a predisposal to diseases. Research has shown the potential of different nutritional strategies to reduce the production of pro-inflammatory cytokines, with the main goal to manipulate health and performance of pigs. Promising examples of nutritional strategies are fungal fermented products and their derivatives which are described to contain several compounds that may play a role in gastrointestinal health and pathogenic bacteria control. Products from Agaricus subrufescens mushroom are reported to contain prophylactic and therapeutic properties including antimicrobial and immunomodulatory properties. RESULTS: This study analysed the post-weaning immune status in intestinal tissue and blood of piglets, with the objective to evaluate the gastrointestinal health and immune modulation response induced by a blend of mannan-rich hydrolyzed copra meal and fermented rye with A. subrufescens. Intestinal histomorphology demonstrated a villus height reduction in jejunum and increase in ileum on day 15, while increased villous height in jejunum and ileum on day 30. The results showed that in post-weaning piglets, the feed additive stimulates an immunomodulation effect most evident at 15 days post-weaning, with significant lower expression of cytokines Interferon (IFN) γ, Interleukin (IL) 1α, IL-1ß, IL-6, IL-8, IL-10 and Transforming Growth Factor (TGF) ß in jejunum, accompanied with an increase in peripheral blood mononuclear cells (PBMC) cytokine gene expression of IL-1ß, IL-6, IL-8, IL-10, IL-12p35 (IL-12α), IL-12p40 (IL-12ß), Tumor Necrosis Factor (TNF) α, IFN-α, and TGF-ß. In piglets fed the feed additive, the quantity of Immunoglobulin (Ig) A producing cells in jejunum, ileum was reduced on day 15 and 30 post-weaning, and on day 30 and 45 post-weaning in colon tissue. Natural Killer (NK) cells count in blood were increased on day 15 post-weaning in the piglets fed the feed additive. CONCLUSION: This study implies the potential of the blend including mannan-rich hydrolyzed copra meal and fermented rye with A. subrufescens on immune modulation in the intestine of post-weaning piglets.

Altered Proteomic Profile of Adipose Tissue-Derived Mesenchymal Stem Cell Exosomes from Cats with Severe Chronic Gingivostomatitis.

Feline chronic gingivostomatitis (FCGS) is a pathology with a complicated therapeutic approach and with a prevalence between 0.7 and 12%. Although the etiology of the disease is diverse, feline calicivirus infection is known to be a predisposing factor. To date, the available treatment helps in controlling the disease, but cannot always provide a cure, which leads to a high percentage of refractory animals. Mesenchymal stem cells (MSCs) play a pivotal role in the homeostasis and reparation of different tissues and have the ability to modulate the immune system responses. This ability is, in part, due to the capacity of exosomes to play a part in intercellular cell communication. However, the precise role of MSC-derived exosomes and their alterations in immunocompromised pathologies remains unknown, especially in veterinary patients. The goal of this work was to analyze the proteomic profile of feline adipose tissue-derived MSCs (fAd-MSCs) from calicivirus-positive FCGS patients, and to detect possible modifications of the exosomal cargo, to gain better knowledge of the disease's etiopathogenesis. Using high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology, exosomes isolated from the fAd-MSCs of five healthy cats and five calicivirus-positive FCGS patients, were pooled and compared. The results showed that the fAd-MSCs from cats suffering from FCGS not only had a higher exosome production, but also their exosomes showed significant alterations in their proteomic profile. Eight proteins were exclusively found in the exosomes from the FCGS group, and five proteins could only be found in the exosomes from the healthy cats. When comparing the exosomal cargo between the two groups, significant upregulation of 17 and downregulation of 13 proteins were detected in the FCGS group compared to the control group. These findings shed light on new perspectives on the roles of MSCs and their relation to this disease, which may help in identifying new therapeutic targets and selecting specific biomarkers.

Immunometabolism Modulation in Therapy.

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions.

Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction.

A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.

Weaning causes a prolonged but transient change in immune gene expression in the intestine of piglets.

Controlling gut inflammation is important in managing gut disorders in the piglet after weaning. Establishing patterns of inflammation markers in the time subsequent to weaning is important for future research to determine whether interventions are effective in controlling gut inflammation. The objective of this study was to evaluate the intestinal inflammatory response during the postweaning period in piglets. A 45-d study included 108 piglets (weaned at 22 d, body weight 5.53 ± 1.19 kg), distributed in 12 pens with nine pigs per pen. Histomorphometry, gene expression of pro- and anti-inflammatory cytokines, and the quantity of immunoglobulin (Ig) A producing cells were measured in jejunum, ileum, and colon on days 0, 15, 30, and 45 postweaning. Cytokine gene expression in peripheral blood mononuclear cells and Ig quantities were analyzed in blood from piglets on days 0, 15, 30, and 45 postweaning. Histomorphometrical results showed a lower villus length directly after weaning. Results demonstrated a postweaning intestinal inflammation response for at least 15 d postweaning by upregulation of IgA producing cells and IFN-γ, IL-1α, IL-8, IL-10, IL-12α, and TGF-ß in jejunum, ileum, and colon. IgM and IgA were upregulated at day 30 postweaning. IgG was downregulated at day 15 postweaning. The results indicate that weaning in piglets is associated with a prolonged and transient response in gene expression of pro- and anti-inflammatory cytokines and IgA producing cells in the intestine.

Impacto de la vacunación frente a tosferina en España: informe de la sesión científica extraordinaria celebrada en la Real Academia Nacional de Medicina (28/09/2020) / Impact of whooping cough vaccination in Spain: report from the extraordinary scientific meeting held at the Royal National Academy of Medicine. September 28th, 2020

La Real Academia Nacional de Medicina celebró en septiembre 2020 la sesión científica extraordinaria "Impacto de la vacunación frente a tosferina en España". La incidencia de tosferina ha aumentado a nivel mundial desde 2010. El alarmante incremento de hospitalizaciones relacionadas con la tosferina especialmente en niños menores de 1 año promovió la toma de decisiones orientadas a mejorar su protección. En 2014 la Organización Mundial de la Salud recomendó la vacunación durante el embarazo para proteger a los recién nacidos hasta que pudieran completar la primovacunación. En España, esta medida se implantó en 2016 y desde entonces se ha registrado una disminución significativa de hospitalizaciones y de muertes en niños menores de 1 año. La implantación de estrategias apropiadas de inmunización, el reconocimiento de la importancia de la vacunación a lo largo de toda la vida y la investigación en vacunas de mayor eficacia son claves para un control global de la tosferina

The Royal National Academy of Medicine of Spain held a special session on "The impact of vaccination against pertussis in Spain" in September 2020. The incidence of pertussis worldwide has increased since 2010. The alarming increase in the rate of hospitalization among children younger than 1 year of age prompted decisions aimed at improving their protection. In 2014, the World Health Organization recommended vaccination during pregnancy to protect newborns until they could complete the primary series of vaccinations. In Spain, this measure was implemented in 2016 and, since then, a significant drop in hospitalization and deaths among children younger than 1 year has been recorded. The implementation of appropriate immunization strategies, the recognition of the importance of vaccination throughout life, and research into new vaccines with higher efficacy are key to achieving global control of pertussis

Tackling the Threat of Rabies Reintroduction in Europe.

Rabies is one of the oldest, most important zoonoses worldwide due to its extreme and inevitably lethal nature, causing one death every 9 min worldwide. Recent reports have demonstrated that the Lyssavirus continues more alive than ever, despite the control carried out against the virus throughout Europe. In this context, this work reviews the main immunological implications, transmission risk factors and current prevention measures for virus control in Europe, and especially in Spain.

Inmunología y vacunología del meningococo / No disponible

No disponible

Allogeneic adipose-derived mesenchymal stem cell therapy in dogs with refractory atopic dermatitis: clinical efficacy and safety.

Canine atopic dermatitis (AD) is a common skin disease with a 10-15 per cent prevalence. Current treatments vary in their efficacy and safety. The immunomodulatory properties of mesenchymal stem cells (MSCs) make them a promising alternative treatment. The aim of this study was to evaluate the therapeutic efficacy and safety of allogeneic canine adipose MSCs (cAd-MSCs) in dogs with refractory AD. Twenty-six dogs, suffering from AD for at least 12 months, not responding to conventional therapy, received an intravenous dose of 1.5×106 cAd-MSCs/kg bodyweight. Clinical signs, haematological and biochemistry profiles, and AD severity were assessed in a six-month follow-up using a validated scoring system (Canine Atopic Dermatitis Extent and Severity Index, version 4 (CADESI-04)). The degree of pruritus was quantified using a validated visual analogue scale, and also owner's global assessment of treatment efficacy. Twenty-two animals completed the study. Pruritus and CADESI-04 scores decreased significantly after one week or month of treatment, respectively, and remained stable for six months. Owner's global assessment score was 2.15±1.15 for all the animals in the study. In conclusion, systemic administration of allogeneic cAd-MSCs appeared to be a simple therapy with positive outcome in the remission of clinical signs for AD refractory to conventional medications, for at least six months and with no adverse events.

Safety and efficacy of the mesenchymal stem cell in feline eosinophilic keratitis treatment.

BACKGROUND: Feline eosinophilic keratitis (FEK) is a chronic keratopathy caused by a suspected immune mediated response to an unknown antigenic stimulus. The purpose of this study was to investigate the safety and therapeutic effects of allogeneic feline adipose-derived mesenchymal stromal cells (fAd-MSCs) implanted subconjunctival around the ocular surface lesion in five cats with FEK refractory to current available treatments. RESULTS: FEK was diagnosed by clinical appearance and evidence of eosinophil and/or mast cells in corneal cytology. Each animal was treated with two applications of 2 × 106 million of fAd-MSCs 2 months apart. Ocular surface integrity was assessed before treatment and at 1, 3, 6 and 11 months after treatment. Clinical signs showed a significant change during the follow-up with resolution of the corneal and conjunctiva lesions and there were no signs of regression or worsening. CONCLUSIONS: Implanted cells were well-tolerated and effective reducing clinical signs of FEK with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that local implantation of allogeneic fAd-MSCs has been found as an effective therapeutic alternative to treat cats with FEK.

First report of Leishmania infantum infection in the endangered orangutan (Pongo pygmaeus pygmaeus) in Madrid, Spain.

BACKGROUND: Some wild animals have been recognized as potential reservoirs of Leishmania infantum infection (e.g. carnivores, lagomorphs, rodents, etc.). Leishmania infantum was also identified infecting humans and lagomorphs (i.e. hares and rabbits) over the period of 2009-2016, with the latter acting as the main reservoirs involved in the human leishmaniosis outbreak in Madrid. RESULTS: Two cases of clinical leishmaniosis are reported in orangutans (Pongo pygmaeus pygmaeus) housed at two different centres in Madrid. The first is the case of a 36-year-old male orangutan with severe weight loss and apathy. A complete blood count and biochemical profile revealed anaemia, neutropenia, hypoalbuminaemia and elevated transaminases. Hepato-splenomegaly was also observed. Four months later, due to worsening of clinical signs (mainly bilateral epistaxis), blood and bone marrow samples were collected. Amastigotes of L. infantum were detected in macrophages from a bone marrow aspirate and by specific polymerase chain reaction. The second case was a 34-year-old female orangutan with severe weight loss and apathy and no other apparent clinical signs. A complete blood count and biochemical profile revealed anaemia, pancytopenia and hypoalbuminaemia. Splenomegaly and pericardial effusion were also observed. As leishmaniosis was included in the differential diagnosis, both blood and bone marrow samples were collected. Leishmania infantum infection was confirmed by microscopy, molecular diagnosis and serology (immunofluorescence antibody test). Both animals were treated daily with oral miltefosine for 28 days; allopurinol was also given uninterruptedly in Case 2 for at least 6 months. During follow-up, though good clinical recovery was clear, a lack of parasitological cure was confirmed molecularly in both blood and bone marrow samples from the two orangutans. In both habitats, the presence of the sand fly vector identified as Phlebotomus perniciosus was confirmed. CONCLUSIONS: To our knowledge, this is the first report of L. infantum infection in great apes and in the endangered species P. p. pygmaeus. We are presently looking for L. infantum in other non-human primates living in the same peri-urban areas. If detected, we will examine the impacts of this serious disease on these critically endangered species.

Tiroiditis de Hashimoto / No disponible

No disponible

Defensas, emociones y estrés: la ciencia de la psiconeuroinmunología / No disponible

No disponible

La inflamación: amiga o enemiga / No disponible

No disponible

[Disseminated histoplasmosis in a dorcas gazelle (Gazella dorcas neglecta) kept in captivity conditions in Spain]. / Histoplasmosis diseminada en una gacela dorca (Gazella dorcas neglecta) mantenida en condiciones de cautividad en España.

A 17 month old female gazelle dorca (Gazella dorcas neglecta), kept in captivity in a Spanish zoo, showed several symptoms of illness including fever, lethargy and behavioural changes. (X)-ray revealed ruminal "foreign bodies" and pneumonia with a nodular pattern. After surgical intervention, the animal died. At necropsy, histopathologic and microbiological findings were consistent with the diagnosis of disseminated histoplasmosis, with an inflammatory histological pattern associated with immunodepression in the animal, similar to those observed in patients with severe immunodeficiency (AIDS and others).

Histoplasmosis diseminada en una gacela dorca (Gazella dorcas neglecta) mantenida en condiciones de cautividad en España / Disseminated histoplasmosis in a gazelle dorca (Gazella dorcas neglecta) kept in captivity conditions in Spain

Se presenta el caso de una hembra de gacela dorca (Gazella dorcas neglecta) mantenida en condiciones decautividad en un zoológico español. El animal, perteneciente a un lote procedente de un centro de cría encautividad del sureste de Andalucía, comenzó con un cuadro de fiebre, letargia y cambios de comportamiento.Radiológicamente se detectaron varios cuerpos extraños en rumen y, en el tórax la presencia deuna neumonía con patrón nodular. Después de ser intervenida quirúrgicamente murió. En la necropsia, loshallazgos histopatológicos y microbiológicos demostraron la presencia de una histoplasmosis diseminadacon un patrón histológico de respuesta inflamatoria asociado a condiciones de inmunodepresión en el animal,similar a la de personas con graves inmunodeficiencias (sida y otras)(AU)

A 17 month old female gazelle dorca (Gazella dorcas neglecta), kept in captivity in a Spanish zoo, showedseveral symptoms of illness including fever, lethargy and behavioural changes. X-ray revealed ruminal“foreign bodies” and pneumonia with a nodular pattern. After surgical intervention, the animal died. Atnecropsy, histopathologic and microbiological findings were consistent with the diagnosis of disseminatedhistoplasmosis, with an inflammatory histological pattern associated with immunodepression in theanimal, similar to those observed in patients with severe immunodeficiency (AIDS and others)(AU)

Function and occurrence of facial flushing in birds.

So far overlooked as a pigment involved in visual communication, the haemoglobin contained in the blood of all birds is responsible for the red flushing colours in bare skin areas of some species. Our aim has been twofold: (1) to study sub-epidermical adaptations for blood circulation in two flushing species: the crested caracara (Polyborus plancus) and the hooded vulture (Necrosyrtes monachus), and (2) to provide the first compilation of avian species with flushing skin. The bare facial skin of both the caracara and the hooded vulture contains a highly vascularised tissue under the epidermis that may be filled with blood and would thus produce red skin colours. In contrast, feathered areas of the head show very few vessels immersed in connective tissue and have no potential for colour changes. Species with flushing colours are few but phylogenetically diverse, as they belong to 12 different avian orders and at least 20 families. The majority are dark-coloured, large-sized species living in hot environments that may have originally evolved highly vascularised skin patches for thermoregulation. Bird behaviour as well as sex and age differences within species suggest that a signalling system for condition or status based on haemoglobin may have been super-imposed to the physiological process of heat dissipation.

Malondialdehyde: a possible marker of ageing.

BACKGROUND: Numerous recent studies have suggested that oxidative damage may be important in the ageing process, and lipid peroxidation is an important biological consequence of oxidative cellular damage. OBJECTIVE: The aim of this work was to analyze the activities of the two protective enzymes, superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) to examine the relationship between the ageing process and defence antioxidant and lipid peroxidation. METHOD: SOD activity was measured in red blood cells using the Minami and Yoshikawa method; CAT activity was measured in hemolysates by the Aebi method, and MDA levels were measured in erythrocytes by high-performance liquid chromatography. RESULTS: SOD activity shows statistically significant differences between newborns and the rest of the sample (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.001). CAT activity did not show significant differences between the age groups. We observed statistically significant differences in MDA levels between the different groups (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.05). In the regression analysis and rectilinear/curvilinear adjustment compared to age, SOD and CAT showed coefficients close to zero (SOD linear = 0.16; SOD exponential = 0.15; CAT linear = 0.056; CAT exponential = 0.068), indicating in that way their independence from age. Only MDA obtained a regression coefficient superior to 0.75 (p < 0.05). The best adjustment was reached through an exponential expression, giving the following parametric relation: MDA = 103.117e(0.0021.AGE). No statistically significant variation in SOD and CAT activity and MDA levels, related to sex could be demonstrated. CONCLUSIONS: Our data show that old age is associated with an increase in systemic oxidative stress.